A registry-based non-interventional post-authorization safety study to evaluate the long-term safety of dupilumab in children aged ≥6 months to <6 years with moderate-to-severe atopic dermatitis using the PEDISTAD registry: a cohort design

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  DUPIXENT
• Study drug International non-proprietary name (INN) or common name:
  DUPILUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (D11AH05) dupilumab

  dupilumab
• Medical condition to be studied:
  Dermatitis atopic

Population studied

• Short description of the study population:
  Patients aged >=6 months to <6 years with moderate-to-severe atopic dermatitis
• Age groups:
  Paediatric Population (< 18 years)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)
• Estimated number of subjects:
  515

Study design details

• Study design:
  This registry-based PASS is an international, observational, registry-based cohort study, using data collected in the ongoing PEDISTAD registry, which enrolls and follows patients aged <12 years old with moderate-to-severe AD.
• Main study objective:
  Primary objective: To describe the long-term safety of dupilumab in terms of the incidence rate of safety outcomes (adverse events [AEs] and serious adverse events [SAEs]) among patients in the DUPI-All cohort and separately, if sufficient sample size, in the DUPI-Steroid and Pure DUPI sub-cohort. ; ; Secondary Objectives include: ; a) To describe the patient characteristics, severity of AD by clinician assessment and by PROs, medical history and selected comorbidities at index date for patients in the DUPI-All cohort and separately, if sufficient sample size, in the DUPI-Steroid and Pure-DUPI sub-cohorts; ; b) to describe the patient characteristics, severity of AD by clinician assessment and by PROs, medical history and selected comorbidities at index date for the patients in the Other AD therapies cohort.; c) to describe the AD drug utilization up to and after the index date (i.e., initiation date of cohort-defining treatment) for patients in the DUPI-All cohort and the Other AD therapies cohort; ; d) to describe the incidence rate of safety outcomes (AEs and SAEs) among patients in the Other AD therapies cohort.
• Setting:
  Secondary use of data collected in the global Pedistad AD disease registry. All patients are treated according to routine clinical care, and all follow-up conducted as per routine care.; ; The PEDISTAD registry was initiated in September 2018 with an intended prospective follow-up of five years. In 2023, follow-up was extended to 10 years from enrollment. Patients are aged <12 years old with moderate-to-severe AD whose disease is not adequately controlled with topical therapies or for whom those therapies are not medically advisable. During the follow-up period, data are collected at visits that take place as per routine clinical care, planned to take place twice per year, approximately six months apart, which is consistent with typical standard of care in this patient population. Patients are included in the DUPI PEDISTAD-registry-based PASS on the date of initiating a cohort-defining medications (the index date).
• Comparators:
  DUPI-ALL cohort: Initiated treatment with dupilumab, with index date at or after PEDISTAD enrollment date; no restriction based on usage of prior or overlapping “other AD therapies”; aged ≥6 months to <6 years at index date. ; DUPI-Steroid sub-cohort: sub-cohort of the DUPI-ALL cohort; initiated treatment (first ever) with dupilumab, with index date at or after PEDISTAD enrollment date; prior or overlapping use of SCS or high potency TCS at index date - prior or overlapping use of other systemic agents at the index date is not permitted; aged ≥6 months to <6 years at index date. Pure-DUPI sub-cohort: subcohort of the DUPI-ALL cohort; initiated treatment (first ever) with dupilumab with index date at or after PEDISTAD enrollment date; no prior or overlapping use of any "other AD therapy" at index date; aged ≥6 months to <6 years at index date. Other AD therapies cohort: Initiated treatment with SCS, UV therapy, immunosuppressants, JAK inhibitors , other systemic biologic treatments for moderate-to-severe AD (e.g., tralokinumab) or high potency TCS with index date at or after PEDISTAD enrollment date; aged ≥6 months to <6 years at index date. Prevalent Dupilumab Users cohort: receiving ongoing dupilumab treatment at enrollment into the PEDISTAD registry (prevalent users), aged ≥6 months to <6 years at index date.
• Outcomes:
  Safety outcomes (AEs and SAEs), exposure treatment details, patient characteristics, AD disease characteristics, medical history, comorbidities.
• Data analysis plan:
  The primary analysis will include calculation of incidence rates with 95% confidence intervals (CI) presented for AEs and SAEs, overall and categorized by intensity and according to the Medical Dictionary for Regulatory Activities (MedDRA) groupings (e.g., by system organ class (SOC) and/or preferred term (PT)). The incidence rates will be provided for the DUPI-All cohort, and separately if sufficient sample size, the DUPI-Steroid and Pure-DUPI cohorts. The incidence rate will be calculated as the number of events divided by number of exposed person-years and will be expressed as incidence rate per 100 person-years. All events with onset at or after index date will be included and persons-years will be calculated as the time-period (in years) between index date and the end of exposure for each patient. ; For the secondary analyses, the patient characteristics, severity of AD by clinician assessment and patient/caregiver assessment, prior and concomitant diseases will be described among the DUPI-All and Other AD therapies cohorts using descriptive statistics. The AD drug utilization patterns will be described using descriptive statistics as well. Confidence intervals, whenever deemed appropriate, will be 2-sided with a confidence probability of 95%, unless otherwise specified. ; ; Furthermore, the incidence rates of AEs and SAEs with 95% CI, overall and categorized according to MedDRA (for example by SOC and/or PT) and by intensity, will be presented for the Other AD therapies cohort.